tbuckley/cabot-search huggingface dataset:
Systematic review and meta-analysis of accuracy of tumor origin detection in blood cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) assays in the general population.
Authors: Joo Hee Park, Youjin Oh, Liam Il-Young Chung, Richard Duan, Trie Arni Djunadi, Sung Mi Yoon, Zunairah Shah, Chan Mi Jung, Ilene Hong, Leeseul Kim, Horyun Choi, Young Kwang Chae
Journal: Journal of Clinical Oncology (2023)

e15053 Background: Among recently developed blood-based MCED tests, the ability to determine the location of tumors is pivotal to guiding appropriate treatment. We systematically reviewed and statistically examined the accuracy of tumor of origin predictions among blood-based MCED tests. Methods: Original articles were searched from Pubmed, Cochrane, and Embase for blood-based screening tests, multiple cancer types, and asymptomatic human subjects. We excluded studies with small samples (n &lt; 30), non-screening, and non-blood-based tests. For cfDNA-based assays, measurements of diagnostic accuracy were pooled for meta-analysis. Results: Of 1,074 records identified and screened, five case-control studies and one cohort study that used cfDNA-based diagnostic tests were analyzed. Accuracy of tissue-of-origin (TOO) prediction for 3,895 cancer samples across cancer types was 0.79 (95% CI 0.66 - 0.90). Among six cancer types, colorectal cancers had the highest accuracy and liver &amp; bile duct cancers had the lowest, although the difference was statistically insignificant (0.89 (95% CI 0.79-0.97) vs. 0.68 (95% CI 0.40-0.90)). Additionally, cases were most frequently misclassified as colorectal cancer (Table 1). The information for localizing TOO was derived from methylation patterns of cfDNA in four studies, fragmentation profiles of cfDNA in another study, and combination of mutations in cfDNA and protein markers in the last study. Conclusions: Our results demonstrate that the primary site of cancers was accurately discerned in 79% of cases by MCED tests. However, performance varies across cancer types. Further research on performance based on cancer stages and in combination with other molecular profiling is warranted. [Table: see text]
Association of host immune signatures with response to immunotherapy-based regimens in patients with metastatic renal cell carcinoma (mRCC).
Authors: Eddy Saad, Chris Labaki, Renee Maria Saliby, Li Song, Ziad Bakouny, Wenting Pan, McKenzy Wall, Gwo-Shu Mary Lee, David A. Braun, Xiaole Shirley Liu, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2023)

4550 Background: Treatment options for mRCC have evolved to include VEGF targeted therapies (VEGF-TT), immune checkpoint inhibitors (ICIs), or combinations of both. The interaction between the tumor and its immune microenvironment has been shown to influence clinical outcomes in patients treated with immunotherapy-based regimens. The aim of this study was to characterize the T-cell and B-cell immune repertoires in patients with mRCC treated with VEGF-TT, ICI or a combination of both, and evaluate their associations with clinical outcomes. Methods: We identified patients with mRCC at Dana-Farber Cancer Institute treated with VEGF-TT, ICI or both, and for whom tumor and/or blood samples were available. Bulk RNA-sequencing (RNA-seq) and T-cell receptor sequencing (TCR-seq) were performed on peripheral blood mononuclear cells (PBMCs), collected before and during therapy. Bulk RNA-seq was additionally performed on available pre-treatment primary tumor samples. Immunoglobulin heavy chain (IgH) isotypes were inferred from bulk RNA-seq data using TRUST4. Parameters of the T-cell and B-cell repertoires were evaluated in responders vs. non-responders to systemic therapies, and between pre- and on-treatment samples within patient subgroups. Results: In total, blood (PBMC) samples from 386 patients were available across all treatment cohorts. Following quality-control, TCR-seq and RNA-seq data were available for 367 and 134 patient samples, respectively. Responders to ICI-based regimens (ICI or VEGF-TT+ICI) presented a trend towards an increased baseline (pre-treatment) TCR clonality as compared to non-responders (p=0.06), corresponding to a less polyclonal T cell repertoire in responders at baseline. No significant changes in clonality were seen between pre- and on-treatment samples among responders to ICI regimens (p=0.14), as opposed to non-responders where a significant increase was identified (p=0.001). The analysis of IgH isotypes in baseline blood samples showed higher fraction of IgG1 in responders (vs. non-responders) to ICI regimens (p=0.01). This was further confirmed in the analysis of IgH isotypes inferred from tumor samples (p=0.04). No significant differences in IgH isotype fractions were identified between responders and non-responders to VEGF-TT. Conclusions: We were successfully able to characterize T-cell receptor and IgH repertoires in a large cohort of patients with mRCC and evaluate their associations with ICI response. Our results show that baseline TCR clonality and IgG1 antibody fraction are associated with the response to ICI regimens, suggesting a potential role for immune biomarker development.
Liquid-biopsy detection of FGFR2 and other actionable rearrangements in GI malignancies.
Authors: Pashtoon Murtaza Kasi, Jessica Kim Lee, Hanna Tukachinsky, Lincoln W Pasquina, Pierre Vanden Borre, Brennan James Decker, Dean C. Pavlick, Justin Allen, Christine Parachoniak, Alexa Betzig Schrock, Christine M. Lovly, Geoffrey R. Oxnard, Vivek Subbiah
Journal: Journal of Clinical Oncology (2023)

4085 Background: Actionable rearrangements (RE) represent an emerging therapeutic target for GI malignancies. However, there remains uncertainty whether liquid biopsy (LBx) assays testing circulating tumor DNA (ctDNA) can detect RE with the same fidelity as tissue biopsy. Here we report the performance of ctDNA-based comprehensive genomic profiling (CGP) for the detection of RE leveraging an FDA-approved &gt;300-gene platform, with a focus on data from patients with GI malignancies. Methods: An institutional research database of clinical CGP results for tissue biopsy (TBx, FoundationOneCDx) and LBx (FoundationOneLiquid CDx) from patients with cancers of the GI tract was reviewed. Sensitivity for FGFR2 RE was studied in patients with cholangiocarcinoma (CCA) or carcinoma of unknown primary (CUP) and both TBx and LBx CGP available. Results: Across 7870 GI LBx, 1094 predicted pathogenic RE were detected in 826 cases (10%) including 283 oncogenic kinase RE, 686 inactivating RE, and 125 other gain-of-function RE. FGFR2 was the most frequently rearranged gene, enriched in CCA (4.4%, 37/833) and stomach (3.0%, 11/368). EGFR RE (38) occurred across 6 cancer types and included 8 fusions, 15 c-terminal truncations, 4 intragenic deletions/inversions, and 3 kinase domain duplications. BRAF RE (31) were detected among in colorectal (22) and pancreas (9) cases. LBx detected 44 exon 3 skipping (protein stabilizing) RE in CTNNB1 (beta-catenin) across all samples. Other frequent activating RE were detected in MYC (36), FGFR3, RET, ROS1 (21 each), and ALK (13). Potentially targetable inactivating RE were detected in BRCA1 (28), ARID1A (24), STK11 (22), PTEN (17), TSC2 (14), and BRCA2 (8). Focusing on CCA, FGFR2 RE were more prevalent in cases with elevated (≥1%) ctDNA tumor fraction (TF, 26/342, 7.6%), matching the prevalence in TBx (7.8%, 505/6,492) with a similar spectrum of fusion partners seen for both TBx and LBx (30% BICC1, 70% rare for both). In 13 CCA/CUP patients positive for FGFR2 RE by TBx, LBx detected 12 (92%) including 8 different fusion partners; the false negative case had TF &lt;1%. In 11 CCA LBx samples with FGFR2 resistance mutations detected, LBx CGP successfully detected a driver FGFR2 RE in 10 and driver C382R mutation in 1. Conclusions: Rearrangements are represented across GI malignancies, including many that result in known oncogenic drivers that may be targetable with available therapies. We observe reliable detection of FGFR2 fusions in ctDNA, in contrast to some prior publications. ctDNA represents a pragmatic analyte for detection of rearrangements and other actionable alterations, offering timely result return when tissue is inadequate or unavailable. [Table: see text]
Neoadjuvant camrelizumab plus chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A single-arm, phase II trial.
Authors: Jin Gao, Liting Qian, Lingran Zhou, Bin Sun, Jian He, Ru Wang, Yangyang Zhang, Liping Yang, Yan Zhou, Jing Yang
Journal: Journal of Clinical Oncology (2023)

e18057 Background: Anti-programmed death receptor-1 (PD-1) agents improve survival in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC), but have not been studied well in patients with locoregionally advanced NPC. In this study, we investigated the efficacy and safety of the PD-1 inhibitor camrelizumab combined with gemcitabine and cisplatin as neoadjuvant therapy in patients with locoregionally advanced NPC. Methods: This was a single-arm, single-center, phase II trial done at the First Affiliated Hospital of University of Science and Technology of China. Patients with previously untreated, stage III-IVB (except T3N0-1; AJCC 8th) NPC, aged 18-70 years without severe comorbidities were enrolled. Eligible patients received neoadjuvant therapy with camrelizumab 200 mg on day 1, cisplatin 80 mg/m 2 on day 1, and gemcitabine 1,000 mg/m 2 on days 1 and 8 of each 21-day cycle for three cycles. The primary endpoints were overall response rate(ORR) per RECIST version 1.1 and safety. Biomarker analysis included programmed death-ligand 1 (PD-L1) expression using the tumor proportion score (TPS) and combined positive score (CPS; Dako 22C3 pharmDx assay). Results: Between January 2022 and January 2023, 14 patients were enrolled and treated. The median age was 55 years (range, 33-68), and 11 (78.6%) patients were males. Thirteen (92.9%) patients had baseline PD-L1 data: TPS ranged from 2% to 80% and CPS ranged from 5 to 90. Eight patients (61.5%) had PD-L1 TPS of higher than 20% and seven patients (53.8%) had PD-L1 CPS of higher than 50. The ORR was 92.9% (13 of 14), including one (7.14%) patient with complete response and 12 (85.7%) patients with partial response. The most common grade 3 treatment-related adverse events (TRAEs; Common Terminology Criteria for Adverse Events, version 5.0) during neoadjuvant treatment were anorexia (two of 14;16.7%) and nausea (two, 9.5%), and no grade 4 or 5 TRAEs occurred. The most common immune-related AEs were endocrinopathies (all grade 1; 50%). Conclusions: Neoadjuvant camrelizumab plus chemotherapy showed promising activity with a manageable safety profile for patients with locoregionally advanced NPC. Longer follow-up and larger studies are needed to further confirm the efficacy of this combination in this population. This trial was approved by the Ethics Office of the First Affiliated Hospital of the University of Science and Technology of China (2021 no98), and registered in the Chinese Clinical Trial Registry. Clinical trial information: ChiCTR2200057745 .
Genomic analysis of RAS and BRAF mutation in an oncology reference hospital in Brazil.
Authors: Guilherme Amorim, Maria Clara Rodrigues Lima Medeiros, Mariana Ferreira, Ana Maria Rodrigues Lima Medeiros, Bruna Bighetti, Nora Manoukian Forones, Hakaru Tadokoro
Journal: Journal of Clinical Oncology (2023)

e15545 Background: Colorectal cancer (CRC) is a common malignancy worldwide and a leading cause of cancer-related deaths. The molecular basis of CRC can guide patient prognosis and therapy. Unfortunately, knowledge on the CRC mutation landscape is limited. In this study, we investigated the mutation profile of related genes by next-generation sequencing and associated with microsatellite instability (MSI) in a series of 43 Brazilian CRC patients from 2016 to 2022, of a Public Oncology Hospital. This study aimed to analyze the frequency of mutation covariates of the KRAS and BRAF genes and their correlation with survival data in patients diagnosed with metastatic RCC. Methods: We conducted a retrospective, observational and descriptive study in 43 patients diagnosed with CRC treated at an Oncology Reference Hospital in Brazil. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissues. Targeted sequencing was performed using a customized panel for CRC-related genes. The mutation data was analyzed in relation to clinicopathological features, MSI status and survival, using the Kaplan-Meier method and log-rank test. Results: RAS mutations were found in 37.2% of patients and BRAF mutations in 9.3%. The analysis of most secondary clinicopathological features did not show statistical prognostic impact. In general analysis, the age and presence of BRAF mutation were related to the increased risk of death HR-0.31 (0.11-0.82). However, among patients with BRAF mutations exclusively, the age did not represent an increased risk of death. Concerning our RAS mutations, as we already knew from previous literature data, the variety is diverse. We noticed nine different RAS alterations, in which the most prevalent was the G12D (33%), followed by G13D, Q61K and G12A. The distribution of our RAS alteration and prevalence is summarized in the table below: Conclusions: Our findings are consistent with previous studies concerning frequency and patterns of RAS and BRAF mutations in CRC. The identification of MSI and the evaluation of genetic ancestry may help to guide treatment decisions in CRC patients. At present, it is already known that some of RAS mutations are targets for selective RAS drugs and may have better outcomes the pan-RAS drugs. Our study provides important insights into the mutation profile of related genes in Brazilian CRC patients and these findings have implications in clinical management of CRC. Further studies with larger cohorts are needed to validate our findings. [Table: see text]
Comparison of bevacizumab plus doublet chemotherapy regimens in patients with metastatic or recurrent ovarian cancer.
Authors: Nijat Khanmammadov, Izzet Dogan, Pinar Saip, Adnan Aydiner
Journal: Journal of Clinical Oncology (2023)

e17537 Background: Ovarian cancer is the most common cause of death due to gynecological malignancies. Although the primary treatment is surgery, there are different chemotherapy regimens that can be used in metastatic disease. In this study, it was aimed to compare doublet chemotherapy regimens in combination with bevacizumab in patients with metastatic ovarian cancer. Methods: Our study was designed as a retrospective observational study. The clinical, pathological, radiological, and treatment characteristics of the patients were recorded. Survival analyzes were performed using the Kaplan-Meier method, and multivariate analysis using cox regression analysis. Results: 198 patients were included in the study. Median follow-up period after bevacizumab was 18.7 months. The most common pathological subtype was serous carcinoma (%85.9). Before bevacizumab treatment, 96% of patients received perioperative chemotherapy. The most common sites of metastasis were the peritoneum (94.5%), liver (43.9%), lung (18.7%), bone (4.5%), and brain (3%). In combination with bevacizumab, 92 (46.4%) patients used gemcitabine + carboplatin, 76 (38.4%) patients used paclitaxel + carboplatin, and 30 (15.2%) patients used gemcitabine + cisplatin. In the whole patient group, the rate of complete response was 18.7%, partial response 56.1%, stable disease 6.6%, and progressive disease 18.7%. The patients received a median of 9 cycles of bevacizumab and a median of 7 cycles of doublet chemotherapy. Median progression-free survival was 11.9 (95% CI, 9.2-14.5) months, and median overall survival was 24.7 (95% CI, 19.9-29.4) months. History of surgery before bevacizumab (p=0.006) and type of doublet chemotherapy (p=0.024) were found to be statistically significant factors affecting overall survival. The presence of brain metastases (p=0.062) had borderline significance. Conclusions: Doublet chemotherapy regimens with bevacizumab have been found to be effective and safe in the treatment of metastatic ovarian cancer in terms of survival. The combination of bevacizumab with gemcitabine + carboplatin was superior to other doublet chemotherapy regimens in terms of overall survival.
Safety and effectiveness of subtotal pelvic peritonectomy for patients with colorectal cancer with limited peritoneal metastasis in pelvic cavity.
Authors: Leen Liao, Jinghua Tang, Binyi Xiao, Wu Jiang, Kai Han, Ling-Heng Kong, Jiehai Yu, Zhi-Zhong Pan, Pei-Rong Ding
Journal: Journal of Clinical Oncology (2023)

e15587 Background: Cytoreductive surgery with extensive visceral resection and peritonectomy has shown long-term survival benefits for colorectal cancer (CRC) patients with peritoneal metastasis. However, the extent of peritonectomy remains controversial for limited peritoneal metastasis. This study modified the selective pelvic peritonectomy (SPP) to subtotal pelvic peritonectomy (STPP) for patients with limited peritoneal metastasis in pelvic cavity, and aimed to assess the outcome of STPP. Methods: CRC patients with limited peritoneal metastases in pelvic cavity and underwent R0 resection were included from a prospectively collected database. Grade III/IV morbidity rate, disease free survival (DFS) and overall survival (OS) were analyzed. Results: A total of 51 patients were included (22 in the STPP group and 29 in the SPP group). An average of 60 minutes increased in operative time in the STPP group, but no perioperative mortality occurred. Grade III/IV complication rates did not differ between two groups. At a median follow-up of 38.1 months, the 3-year-DFS was 63.0% in the STPP group and 29.3% in the SPP group ( P = 0.006). The 3-year-OS was 82.6% and 55.6% for the STPP and SPP groups, respectively ( P = 0.033). Moreover, STPP was independently associated with improved DFS. Eight (38.1%) cases with remaining ovaries developed ovarian metastasis, of whom 6 (75%) underwent a second operation. Conclusions: Subtotal pelvic peritonectomy is associated with promising long-term outcome in CRC patients with limited peritoneal metastasis in the pelvic cavity. Prophylactic bilateral oophorectomy should be strongly considered during this procedure.
How patient-clinician education can strengthen partnerships and promote tangible actions to improve clinical trial diversity in breast and lung cancer trials.
Authors: Tariqa Ackbarali, Ricki Fairley, Susan Thomas Vadaparampil, Aaron Elliott Lisberg, Raymond U. Osarogiagbon, Monique Gary
Journal: Journal of Clinical Oncology (2023)

6510 Background: Some of the greatest disparities in cancer care are related to clinical trial access for our patients. To address the racial/ethnic disparities in breast and lung cancer clinical trials, a tethered educational initiative was designed to empower patients, assess current clinician perceptions/practices, and improve awareness of real-world perspectives of clinical trials. Methods: Two, one-hour online, interactive, video-based programs were designed for patients, caregivers, and providers. This patient/caregiver program was hosted on CancerCoachLive and MedLive in November, 2022, while the provider program was hosted on ClinicalSeriesLive in December, 2022 and will remain on-demand until December 2023. This initiative was conducted in collaboration with TOUCH, the Black Breast Cancer Alliance, BlackDoctors.org, Moffitt Cancer Center, CancerCare, and the Lung Cancer Research Foundation. Herein, we report on an analysis from patients and providers regarding clinical trial diversity, behavioral impact, and qualitative insights. Results: As of data cut-off (02/10/23), 1,425 participants have engaged across both educational programs. Of participating patients, 46% were non-White (non-Hispanic), 36% were in remission, 36% were not on active treatment, and 29% were newly diagnosed. Following the program 81% were motivated to take one or more actions over the next two months: the most common actions being to research clinical trials (38%) or discuss clinical trials with a clinician (19%). Post-activity, 79% were confident to very confident discussing clinical trials with a clinician. Critical data related to clinician preferences was assessed and demonstrated a 23% increase in confidence from pre- to post-activity in improving diversity in clinical trial participation with preferences observed in both breast and lung cancers to offer clinical trials for newly diagnosed and second recurrence settings. Of those who are being offered clinical trials in the community setting, there was a higher likelihood for patients to be offered a clinical trial if their subtype was HER2+ breast cancer subtype or NSCLC with an actionable mutation. Data collection continues as this initiative is ongoing. Qualitative data including clinician write-in examples of behavioral impact and patient perspectives from the interviews will be shared. Conclusions: The outcomes discussed herein reveal a willingness from patients/caregivers to engage in clinical trial discussions and participate in clinical trials, if eligible. These educational programs positively impacted clinician motivation to address barriers to enrollment and clinical trial eligibility with their patients. Real-world accounts of patient experiences provide different perspectives that can help improve approaches to improve clinical trial diversity.